The Ethics and Governance of Human Genetic Databases European Perspectives Part 9 potx

the Human Genome Project has given rise to stronger rhetoric than the

databases, not least around the scientific breakthrough of the Human

Genome Project which was fabricated for the media on 27 June 2000.

When Newsweek published a story on the anticipated breakthrough, more

than two months before it took place, it said: ‘And science will know the

blueprint of human life, the code of codes, the holy grail, the source code

of Homo Sapiens. It will know, Harvard University biologist Walter

Gilbert says, ‘‘what it is to be human’’.’2

The rhetoric used for justification of both the Human Genome Project

and human genetic databases relies in large part on a very simplistic,

deterministic view of genes, which developed alongside the rise of gene￾tics in the twentieth century, but does not quite fit the view of genes in

current science. The history of the concept of the gene is not very old.

When Gregor Mendel published his laws of heredity in 1866 he called the

carriers of hereditary traits simply factors.3 While his paper lay largely

unnoticed in Verhandlungen des naturforschenden Vereines in Bru¨nn, bio￾logists were observing for the first time curious threads in the cell nucleus

when the cell is about to divide. Observations in 1877 of cell division, and

of the formation of the ovum and the sperm cell, soon indicated that the

threads were likely involved in carrying hereditary traits. The threads

were called chromosomes. In 1892, the German physiologist August

Weismann claimed in his Das Keimplasma that the chromosomes con￾sisted of particles which were the carriers of hereditary traits. He called

these particles determinants. Only in 1909 were the carriers of hereditary

traits named genes, by the Danish Mendelian Wilhelm Johannsen,4

although he did not think they were particles. And, as it turned out, no

such particles exist.

Before the 1950s, the interior of the cell nucleus was not well under￾stood. Deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) had

been identified in the late nineteenth century and a little later so were

their four essential components (adenine, thymine, cytosine and guanine,

better known by their initials A, T, C and G). The DNA was believed to

be a repetitive and boring molecule, a ‘stupid’ molecule incapable of the

complexity and diversity required for the carrier of hereditary traits.

2

S. Begley, ‘Decoding the Human Body’, Newsweek, 10 April 2000, p. 52.

3 Most of the historical material in this paragraph and the next is from Horace Freeland

Judson, ‘A History of the Science and Technology Behind Gene Mapping and

Sequencing’, in Daniel J. Kevles and Leroy Hood (eds.), The Code of Codes: Scientific

and Social Issues in the Human Genome Project (Cambridge, MA: Harvard University Press,

1992), pp. 37–42.

4

Jonathan Harwood, Styles of Scientific Thought: The German Genetics Community

1900–1933 (Chicago: University of Chicago Press, 1993), p. 35.

228 Gardar A´rnason

Proteins got everyone’s attention, as they were known to have a complex

structure. Then two things happened. First, Erwin Chargaff published a

paper in 1950 in which he showed that DNA molecules could be ‘as

specific in sequence as proteins’.5

Second, in the spring of 1953 James D.

Watson and Francis Crick published their model of the structure of

DNA, the famous double helix, suggesting that genes are a segment of

DNA sequence and, furthermore, that the DNA both carries hereditary

traits from parents to offspring and is the basis for their expression in the

individual organism.

The gene, as a theoretical entity, kept changing as the theory of genes

changed. The genes of molecular genetics are as far removed from the

genes of classical genetics as the atoms of modern physics are from the

atoms of Leucippus and Democritus. But what are genes today?

One of the most important books on the Human Genome Project,

Kevles and Hood’s The Code of Codes, defines in a glossary the term ‘gene’

thus: ‘The fundamental physical and functional unit of heredity. A gene is

an ordered sequence of nucleotides [A, T, C and G] located in a partic￾ular position [locus] on a particular chromosome. Each gene encodes a

specific functional product, such as a protein or RNA molecule.’6 This

definition is commonplace and simple, but not without problems.

Compare it with the definition of ‘allele’ from the same source: ‘One of

several alternative forms of a gene occupying a given locus on the chro￾mosome. A single allele for each locus is inherited separately from each

parent, so every individual has two alleles for each gene.’7 According to

the definition of a gene above, a gene is a sequence of nucleotides at a

locus, but according to the definition of an allele, an allele is a sequence of

nucleotides at a locus and a gene is a type of similar alleles (or a set of

alleles defined by their function or locus). On the one hand we have the

gene as an abstract entity and on the other its physical instantiation or

encoding in an allele.

This ambiguous use of the term ‘gene’ is common in molecular bio￾logy. In population genetics, ‘gene’ is variously used to refer to an allele or

a locus. This branch of genetics could easily do without ‘genes’ and refer

only to alleles and loci.8

Sometimes a gene seems to be determined by its

function rather than locus or physical encoding in an allele. In a Newsweek

article we read: ‘Most women have two copies of the gene for HER-2

[a receptor protein found on the surface of breast cells], but roughly a

5

Judson, ‘A History of Gene Mapping and Sequencing’, p. 53.

6 Kevles and Hood, The Code of Codes, p. 379. 7

Ibid., p. 375.

8

See Sahotra Sarkar, Genetics and Reductionism (Cambridge: Cambridge University Press,

1998), p. 6.

Genetics, rhetoric and policy 229

third of advanced breast-cancer patients have extra copies of the gene

scattered about chromosome 17.’9

The ontology of genes does occasionally go beyond the ambiguous to

the curious or downright bizarre, at least in popular accounts of genetic

research. Consider cystic fibrosis, which is the most common heredi￾tary disease in Caucasians. Francis S. Collins, Lap-Chee Tsui and Jack

Riordan are often credited with having found ‘the gene for’ cystic fibrosis

in 1989.10 This ‘gene’ is a mutation called delta 508, it is found in 70%

of cystic fibrosis patients and it consists of three base pairs (i.e., three

pairs of nucleotides) that are missing from a locus on chromosome 7.11

This gene is not a sequence of nucleotides, it is nothing physical at all.

At most it is a locus where there should be three base pairs – which are not

there. To be precise, there is a specific genetic explanation for 70% of

all cystic fibrosis cases, namely that three specific base pairs are missing

from a certain locus on both copies of chromosome 7. For the remaining

30% of cystic fibrosis cases, more than 350 pathogenetic mutations have

been found.12 Given all this, it does seem odd to speak of ‘the gene

for’ cystic fibrosis. As far as inherited traits go, cystic fibrosis is simple.

Each time when the disease is expressed in an individual it can be

explained in terms of a single mutation, inherited in a Mendelian fashion

from both parents (this applies at the very least to all cystic fibrosis

patients who have one of the known mutations). Still, there is no ‘physical

and functional unit of heredity’ which corresponds to ‘the gene for

cystic fibrosis’.

The concept of the gene is defined in many different ways depending

on the purpose of the definition, and there is no single way to give a

‘correct’ definition of the gene. Furthermore, the gene as it was imagined

in the early days of genetics, as particles or distinguishable units, simply

does not exist. Despite all this, most people, including scientists, seem to

believe that there are things in nature which we label ‘genes’ and that they

do all sorts of things. A deterministic view of genes seems very common,

except when philosophers and scientists seriously discuss genetic deter￾minism, when no one will admit to holding deterministic views about

9 Geoffrey Cowley and Anne Underwood, ‘A Revolution in Medicine’, Newsweek, 10 April

2000, p. 62.

10 See, for example, Michael Legault and Margaret Munro, ‘Gene Hunters Extraordinaire’,

National Post, 16 March 2000.

11 Nancy Wexler, ‘Clairvoyance and Caution: Repercussions from the Human Genome

Project’, in Kevles and Hood, The Code of Codes, pp. 211–243, at pp. 224–225.

12 John C. Avise, The Genetic Gods: Evolution and Belief in Human Affairs (Cambridge, MA:

Harvard University Press, 1998), p. 64.

230 Gardar A´rnason